Chemical Design, Synthesis And Biological Evaluoation Of Mutual Prodrug Of Gabapentin With Different Types Of Phenolic And Alcoholic Antioxidants

Abstract

Zahraa B. Mohammed and Tagreed N. Omar

This work concern about finding the best effective way to optimizing therapeutic characteristics of gabapentin, by retarding neuronal and gastrointestinal adverse effects through masking of carboxyl group chemically, and increase its analgesic This is achieved by design and synthesis different types of ester derivatives of gabapentin as mutual pro drugs with some of phenolic and alcoholic antioxidants. Pro moieties like; thymol and eugenol, umbilliferon and some other types of phenolic and alcoholic antioxidant ,with the aim of getting synergistic effect as these antioxidants considered as natural analgesic having analgesic and anti-inflammatory activity. The chemical structures of these compounds were confirmed and characterized using Fourier transform infrared spectroscopy (FTIR), 1H-NMR spectroscopy and some physicochemical parameters . The synthesized final compounds (3a–3g) were tested to evaluate their anti- inflammatory, antifungal and antibacterial activity against gram negative and gram positive bacteria. Anti-inflammatory activity in rats using eggâ€�white induced edema method of inflammation . All of the synthesized compound showed anti-inflammatory activity compared to the control group (dimethyl sulfoxide) and gabapentin ; however eugenol conjugate (3f) and thymol conjugate (3a) demonstrate more significant anti-inflammatory activity than the other derivative. The antibacterial and antifungal activity for these compounds evaluated by well diffusion method and the results revealed that compound 3a have the best antibacterial and antifungal activity